Diisopropylethylamine → 4-(9-butyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 2111358

Reaktionsgleichung

Reaktionsgleichung von HRID 2111358
[CH2:1]([N:5]1[CH2:11][CH2:10][C:9](=[O:12])[N:8]([CH3:13])[C:7]2[CH:14]=[N:15][C:16]([NH:18][C:19]3[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][C:20]=3[O:28][CH3:29])=[N:17][C:6]1=2)[CH2:2][CH2:3][CH3:4].F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)C(C)C)C.[NH2:63][CH:64]1[CH2:69][CH2:68][N:67]([CH3:70])[CH2:66][CH2:65]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH2:1]([N:5]1[CH2:11][CH2:10][C:9](=[O:12])[N:8]([CH3:13])[C:7]2[CH:14]=[N:15][C:16]([NH:18][C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH:63][CH:64]4[CH2:69][CH2:68][N:67]([CH3:70])[CH2:66][CH2:65]4)=[O:25])=[CH:21][C:20]=3[O:28][CH3:29])=[N:17][C:6]1=2)[CH2:2][CH2:3][CH3:4]

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 687386064-(9-butyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acidHCID 178484293HCID 178484293, Verbindung

Produkt 1

HCID 250155374-(9-butyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamideAusbeute 64,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A mixture of 0.08 g (0.0002 mole) of 4-(9-butyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-44a), 0.091 g (0.00024 mole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.052 mL (0.0003 mole) of ethyldiisopropyl amine and 1.0 mL of dimethylformamide was stirred for 5 minutes and then 0.034 g (0.0003 mole) of 4-amino-1-methyl-piperidine was added. The mixture was stirred for 3 hours, then diluted with 10 mL of water plus 2 mL of saturated sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with an acetonitrile-water gradient (20:80-100:0) to give 0.064 g of 4-(9-butyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-44) as a white solid.

Aufarbeitung

  1. stirringThe mixture was stirred for 3 hours
  2. extractionextracted 3 times with 10 mL of ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by C18 reverse phase silica gel chromatography
  8. washeluting with an acetonitrile-water gradient (20:80-100:0)

Quellen und Nachweise

ORD-Eintrag
ord-64654fda359f46bea31c24c9c0821036
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07517873B2

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